Anti-mCD8-mIgG2a InvivoFit™ is a mouse anti-mouse monoclonal antibody (mAb) featuring the variable region of the previously described anti-mCD8 YTS 169.4 clone [1]. Using recombinant technology, the original YTS 169.4 rat IgG2b constant region has been replaced with a murine IgG2a format which mediates potent cytotoxic functions [2].
CD8 is a transmembrane protein primarily expressed on most thymocytes and highly expressed by the peripheral mature CD8+ T cell population [3, 4]. Two isoforms CD8α (Lyt-2) and CD8β (Lyt-3) are usually co-expressed and form a CD8α/β heterodimer that plays a critical role in CD8+ T cell development and activation. Other immune cells, such as Natural Killer cells and subsets of dendritic cells also express CD8α [5].
The anti-mCD8 YTS 169.4 mAb is commonly used for in vivo depletion of the CD8+ T cell population to study its role in various immune responses, including in a viral or tumoral context [6-8]. Depending on the nature of the experiment, extended treatment schedules (up to several months) may be required. Upon repeated injection of a xenogeneic mAb, mice produce anti–species antibodies, causing the removal of the administered mAb from circulation, thereby reducing its in vivo efficacy. Moreover, this immunogenicity can lead to fatal hypersensitivity reactions [9-10] which can be reduced by mAb murinization [11].
Key features of Anti-mCD8-mIgG2a InvivoFit™:
- Derives from the YTS 169.4 clone, rat IgG2b, κ
- Features the mIgG2a isotype (constant region)
- Guaranteed sterile, endotoxin level < 1 EU/mg
- Suitable for parental delivery in mice (azide-free)
- Low aggregation < 5%
- Produced in animal-free facilities and defined media
Anti-mCD8-mIgG2a InvivoFit™ is produced in Chinese hamster ovary (CHO) cells, purified by affinity chromatography with protein A, and provided in an InvivoFit™ grade, a high-quality standard specifically adapted to in vivo studies. The specific binding of this mAb to cell surface mCD8α and its in vivo depleting function have been confirmed (see Figures).
References:
- Cobbold S.P. et al., 1984. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 312:548-551.
- Nimmerjahn F. & Ravetch J.V., 2005. Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science. 310(5753):1510-2.
- Fung-Leung W.P. et al., 1991. CD8 is needed for development of cytotoxic T cells but not helper T cells. Cell. 65:443-449.
- Janeway C.A. jr., 1992. The T Cell Receptor as a Multicomponent Signalling Machine: CD4/CD8 Coreceptors and CD45 in T Cell Activation. Annual Rev Immunol. 10:645-674.
- Laky K. & Kruisbeek AM., 2016. In vivo depletion of T lymphocytes. Current Protocols Immunology. 4.1.1-4.1.9. doi: 10.1002/0471142735.im0401s113.
- Greczemiel U. et al., 2020. LCMV-specific CD4 T cell-dependent polyclonal B-cell activation upon persistent viral infection is short lived and extrafollicular. Eur J Immunol. 50:396-403.
- Menares E. et al., 2019. Tissue-resident memory CD8(+) T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells. Nat Comm. 10:4401.
- Vincent-Fabert C. et al., 2019. Reproducing indolent B-cell lymphoma transformation with T-cell immunosuppression in LMP1/CD40-expressing mice. Cell Mol Immunol 16:412–414.
- Mall C. et al., 2016. Repeated PD-1/PD-L1 monoclonal antibody administration induces fatal xenogenic hypersensitivity reactions in a murine model of breast cancer. Onco Immunol. 5(2):e1075114.
- Murphy, J.T. et al., 2014. Anaphylaxis caused by repetitive doses of a GITR agonist monoclonal antibody in mice. Blood. 123(14):2172-2180.
- Belmar N.A. et al., 2017. Murinization and H chain isotype matching of Anti-GITR antibody DTA-1 reduces immunogenicity-mediated anaphylaxis in C57BL/6 mice. J Immunol. 198:4502-4512.